Background: Colorectal cancer susceptibility may correlate with the Klotho gene G-395A and C1818T polymorphisms. This study aims to evaluate the relationship between a Klotho single nucleotide polymorphism and IGF-1 with risk of colorectal cancer.Methods: This study enrolled 60 colorectal cancer patients and 60 age-matched healthy persons who referred to Razi Hospital, Rasht, and Northern Iran in September 2013. Patients enrolled under supervision of a gastro-intestinal specialist and according to the ethics right. G-395A and C1818T polymorphisms were genotyped with polymerase chain confronting two pair primer technology. IGF-1 and certain biochemistry analytes were assayed. Statistical analysis was used to compare appropriate relationships.Results: There were different base pair partitions for G395A and C1818T. Odds ratio and 95% confidence interval were used to analyze the correlation of genotypes and haplotypes with colorectal cancer susceptibility. The AA (odds ratio: 1.437, 95% confidence interval: 0.596) and GA (odds ratio: 1.958, 95% confidence interval: 1.133- 3.385) genotypes of the G-395A polymorphisms showed a slight relationship to the risk of colorectal cancer. The A allele had a much higher frequency in the case group (31.2%) compared with the control group (17.6%). There was no significant relationship with the C1818T polymorphism between the case and control groups.Conclusion: The Klotho gene polymorphism did not significantly increase the risk of colorectal cancer. Therefore, these genotypes might not have a correlation with IGF-1.